The miR-183/96/182 Cluster Regulates the Functions of Corneal Resident Macrophages.
Immunohorizons
; 4(11): 729-744, 2020 11 18.
Article
en En
| MEDLINE
| ID: mdl-33208381
ABSTRACT
Tissue-resident macrophages (ResMÏ) play important roles in the normal development and physiological functions as well as tissue repair and immune/inflammatory response to both internal and external insults. In cornea, ResMÏ are critical to the homeostasis and maintenance, wound healing, ocular immune privilege, and immune/inflammatory response to injury and microbial infection. However, the roles of microRNAs in corneal ResMÏ are utterly unknown. Previously, we demonstrated that the conserved miR-183/96/182 cluster (miR-183/96/182) plays important roles in sensory neurons and subgroups of both innate and adaptive immune cells and modulates corneal response to bacterial infection. In this study, we provide direct evidence that the mouse corneal ResMÏ constitutively produce both IL-17f and IL-10. This function is regulated by miR-183/96/182 through targeting Runx1 and Maf, key transcriptional regulators for IL-17f and IL-10 expression, respectively. In addition, we show that miR-183/96/182 has a negative feedback regulation on the TLR4 pathway in mouse corneal ResMÏ. Furthermore, miR-183/96/182 regulates the number of corneal ResMÏ. Inactivation of miR-183/96/182 in mouse results in more steady-state corneal resident immune cells, including ResMÏ, and leads to a simultaneous early upregulation of innate IL-17f and IL-10 production in the cornea after Pseudomonas aeruginosa infection. Its multiplex regulations on the simultaneous production of IL-17f and IL-10, TLR4 signaling pathway and the number of corneal ResMÏ place miR-183/96/182 in the center of corneal innate immunity, which is key to the homeostasis of the cornea, ocular immune privilege, and the corneal response to microbial infections.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Infecciones por Pseudomonas
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Infecciones Bacterianas del Ojo
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MicroARNs
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Immunohorizons
Año:
2020
Tipo del documento:
Article